EPIC-CP pilot trial study protocol: a multicentre, randomised controlled trial investigating the feasibility and acceptability of social prescribing for Australian children with cerebral palsy.

INTRODUCTION: The social determinants of health contribute to poorer health outcomes for children with cerebral palsy (CP) and are barriers to families accessing health services. At an individual level, social determinants of health are experienced as unmet social needs, for example, unsafe housing conditions. There is emerging evidence that clinical pathways for the systematic identification and referral to services for unmet social needs can support families to address these needs. These clinical pathways have not been implemented for children with CP. The objectives are to investigate the feasibility and acceptability of two co-designed social needs clinical pathways for parents/caregivers of children with CP-social prescribing (ie, Community Linker plus resource pack) compared with resource pack only. METHODS AND ANALYSIS: This pilot randomised controlled trial will run at the three tertiary paediatric rehabilitation services in New South Wales, Australia. A total of 120 participants will be recruited, with randomisation stratified by study site. A survey tool will be used to identify families experiencing unmet social needs. Parents/caregivers who report one or more unmet social need/s and consent will be eligible. The active control group will receive a resource pack containing information on community services to support unmet social needs. The social prescribing intervention group will receive one-on-one Community Linker support, in addition to the resource pack. The survey tool, intervention, logic model, and resource pack were co-designed with patient families and their healthcare workers. Feasibility of the research design and the clinical pathways will be evaluated using the number/proportion of parents/caregivers who complete the survey tool, consent, engage with the intervention, and complete research measures. Acceptability will be evaluated using questionnaires and qualitative interviews. ETHICS AND DISSEMINATION: Human research ethics approval was granted by the Sydney Children's Hospitals Network Human Research Ethics Committee (2022/ETH01688). Participants and stakeholders will receive updates and findings via regular communication channels including meetings, presentations, and publications. TRIAL REGISTRATION NUMBER: Australia New Zealand Clinical Trials Registry: 12622001459718.

Sex Differences in the Broad Autism Phenotype: Insights from the Australian Biobank.

Examining sub-threshold autistic traits in non-autistic first-degree relatives of individuals on the autism spectrum, known as the Broad Autism Phenotype (BAP), could provide new insights into the associations and familial aggregation of autistic traits. This study was a retrospective cross-sectional study of parents (n = 1008), probands with autism (n = 613), and unaffected siblings (n = 221) of probands with autism. BAP traits were examined by the BAP Questionnaire and Communication Checklist-Adult in parents, Autism Developmental Observation Scale-Second edition in probands, and Social Responsiveness Scale in siblings. Multivariable linear regression analyses were used to investigate the associations of parental BAP traits on autistic traits in probands and unaffected sibling BAP traits. Fathers showed significantly increased aloofness, pragmatic language difficulties, and social engagement problems compared to mothers. Female siblings showed increased difficulties with social cognition compared to male siblings. Adjusted models of the regression analyses showed that all BAP traits in fathers were significantly associated with BAP trait expression in probands with autism. Additionally, all of mother's BAP traits were significantly associated with unaffected siblings' BAP trait expression while only fathers' aloofness and rigidity traits were inversely associated with siblings' BAP trait expression. Finally, there were significant inverse interactions noted between parent's BAP traits and their children's BAP trait expression. This study demonstrated differences in how males and females express BAP traits and also identified differences in parent-child associations by sex, with fathers having a greater effect on their proband children's expression of BAP traits than mothers.

The relationship between hair cortisol concentration and autism diagnosis.

BACKGROUND: Autistic children are prone to experience heightened levels of distress and physiological reactivity to a range of sensory, social, and emotional stimuli. In line with this, multiple studies have demonstrated that autistic children have higher acute cortisol stress responses to adverse or threatening stimuli and altered cortisol awakening responses. However, few studies have examined whether this sensitivity may relate to heightened levels of chronic stress and persistently elevated hypothalamic-pituitary-adrenal (HPA) axis activity. The measurement of cortisol accumulation in hair is considered a non-invasive biomarker of chronic stress and has been associated with several childhood diseases. Here, we investigated whether hair cortisol concentration in a large sample of autistic children differed from non-autistic children, and after accounting for a range of child, parental and family-level characteristics. METHODS: Hair cortisol concentration was measured in 307 autistic children and 282 non-autistic controls aged between 2 and 17 years recruited from four Australian states who participated in providing hair samples and demographic data to the Australian Autism Biobank. Independent samples t-test or one-way analysis of variance (ANOVA) were conducted to determine significant differences in the mean hair cortisol concentration (pg/mg) between potential covariates. Primary analysis included multivariable regression modelling of the collapsed sample to identify variables that were significantly associated with hair cortisol concentration after controlling for covariates. We also accounted for the potential interaction of multiple biological (e.g., age, sex, BMI) and psychosocial characteristics at the level of the child, the mother and the father, and the family unit. RESULTS: Our findings suggest that the diagnosis of autism was not a significant predictor of chronic stress, as measured by hair cortisol concentration. However, findings of the multivariable regression analysis showed that key factors such as area of residence (Queensland vs Victorian state of residence) and decrease in child's age were significantly associated with higher hair cortisol concentration whereas lower family income was significantly associated with higher hair cortisol concentration. CONCLUSION: To our knowledge, this is the first study to show that socioeconomic factors such as family annual income affect hair cortisol status in autistic children, indicating that the psychosocial environment may be a potential mediator for chronic stress in autistic children just as it has been demonstrated in non-autistic children.

The search for gastrointestinal inflammation in autism: a systematic review and meta-analysis of non-invasive gastrointestinal markers.

BACKGROUND: Gastrointestinal symptoms and inflammatory gastrointestinal diseases exist at higher rates in the autistic population. It is not clear however whether autism is associated with elevated gastrointestinal inflammation as studies examining non-invasive faecal biomarkers report conflicting findings. To understand the research landscape and identify gaps, we performed a systematic review and meta-analysis of studies measuring non-invasive markers of gastrointestinal inflammation in autistic and non-autistic samples. Our examination focused on faecal biomarkers as sampling is non-invasive and these markers are a direct reflection of inflammatory processes in the gastrointestinal tract. METHODS: We extracted data from case-control studies examining faecal markers of gastrointestinal inflammation. We searched PubMed, Embase, Cochrane CENTRAL, CINAHL, PsycINFO, Web of Science Core Collection and Epistemonikos and forward and backwards citations of included studies published up to April 14, 2023 (PROSPERO CRD42022369279). RESULTS: There were few studies examining faecal markers of gastrointestinal inflammation in the autistic population, and many established markers have not been studied. Meta-analyses of studies examining calprotectin (n = 9) and lactoferrin (n = 3) were carried out. A total of 508 autistic children and adolescents and 397 non-autistic children and adolescents were included in the meta-analysis of calprotectin studies which found no significant group differences (ROM: 1.30 [0.91, 1.86]). Estimated differences in calprotectin were lower in studies with siblings and studies which did not exclude non-autistic controls with gastrointestinal symptoms. A total of 139 autistic participants and 75 non-autistic controls were included in the meta-analysis of lactoferrin studies which found no significant group differences (ROM: 1.27 [0.79, 2.04]). LIMITATIONS: All studies included in this systematic review and meta-analysis examined children and adolescents. Many studies included non-autistic controls with gastrointestinal symptoms which limit the validity of their findings. The majority of studies of gastrointestinal inflammation focused on children under 12 with few studies including adolescent participants. Most studies that included participants aged four or under did not account for the impact of age on calprotectin levels. Future studies should screen for relevant confounders, include larger samples and explore gastrointestinal inflammation in autistic adolescents and adults. CONCLUSIONS: There is no evidence to suggest higher levels of gastrointestinal inflammation as measured by calprotectin and lactoferrin are present in autistic children and adolescents at the population level. Preliminary evidence suggests however that higher calprotectin levels may be present in a subset of autistic participants, who may be clinically characterised by more severe gastrointestinal symptoms and higher levels of autistic traits.

Predicting Communication Skills Outcomes for Preschool Children with Autism Spectrum Disorder Following Early Intervention.

Purpose: This study aims to assess changes in the receptive and expressive language skills and to determine if the baseline characteristics such as communication, cognitive and motor skills, predict outcomes in preschool children with Autism Spectrum Disorder (ASD) following early intervention. Methods: We recruited 64 children participating in the Early Start Denver Model (ESDM) early intervention program at an Autism Specific Early Learning and Care Center (ASELCC) in Australia. Baseline characteristics across various developmental domains was measured using the Mullen Scales of Early Learning (MSEL), Vineland Adaptive Behaviour Scales, 2nd Edition (VABS-II), and the ESDM Curriculum Checklist. Linear mixed-effects models were used to examine the effects of the intervention on outcomes. Fixed-effects such as time, groups (verbal and minimally verbal), and time-by-group interactions were assessed whilst adjusting for covariates. Further, multiple linear regression models were used to determine if the baseline characteristics were significant predictors of the outcomes following the early intervention. Results: Among the 64 children who participated in this study, 38 children were verbal, whereas 26 were deemed to have minimal verbal skills. The mean age of the sample was 4.1 years with a significant male predilection (83%) and from a culturally and linguistically diverse (CALD) background (64%). Findings of the linear mixed effects model showed significant within and between group differences in the ESDM subscales, indicating higher magnitude of changes in the verbal group compared to the minimally verbal group. Finally, the multiple linear regression models suggested that baseline MSEL visual reception and expressive language scores were predictive of changes in the ESDM receptive and expressive communication scores. Conclusion: Understanding a child's baseline skill levels may provide valuable clues regarding what interventions would work best, or which interventions may be less suitable for individual preschool-aged children with ASD.

Saliva DNA: An alternative biospecimen for single nucleotide polymorphism chromosomal microarray analysis in autism.

Chromosomal microarray analysis (CMA) is typically performed for investigation of autism using blood DNA. However, blood collection poses significant challenges for autistic children with repetitive behaviors and sensory and communication issues, often necessitating physical restraint or sedation. Noninvasive saliva collection offers an alternative, however, no published studies to date have evaluated saliva DNA for CMA in autism. Furthermore, previous reports suggest that saliva is suboptimal for detecting copy number variation. We therefore aimed to evaluate saliva DNA for single nucleotide polymorphism (SNP) CMA in autistic children. Saliva DNA from 48 probands and parents (n = 133) was obtained with a mean concentration of 141.7 ng/µL. SNP CMA was successful in 131/133 (98.5%) patients from which we correlated the size and accuracy of a copy number variant(s) called between a proband and carrier parent, and for a subgroup (n = 17 probands) who had a previous CMA using blood sample. There were no discordant copy number variant results between the proband and carrier parent, or the subgroup, however, there was an acceptable mean size difference of 0.009 and 0.07 Mb, respectively. Our findings demonstrate that saliva DNA can be an alternative for SNP CMA in autism, which avoids blood collection with significant implications for clinical practice guidelines.

Sociocultural factors associated with detection of autism among culturally and linguistically diverse communities in Australia.

BACKGROUND: The age at which parents or caregivers first develop concerns about their child's development has significant implications on formal diagnosis and intervention. This study aims to determine the sociocultural factors that are associated with the age and type of first concern reported by parents of autistic children among culturally and linguistically diverse (CALD) communities in Australia. We also assessed whether sociocultural factors predict autism traits measured in terms of social affect (SA), restricted and repetitive behaviours (RRB), and calibrated severity scores (CSS). METHODS: This study is a secondary data analysis of the data collected from six Autism Specific Early Learning and Care Centres (ASELCCs) as part of the Autism Co-operative Research Centre (CRC) program between 2015 and 2019. Data analysed in this study included a family history questionnaire with sociodemographic and sociocultural information, parent-reported age and type of first concern, and clinician/researcher administered Autism Diagnostic Observation Schedule - Second Edition (ADOS-2) which includes standardised domain-wise scores of social affect (SA) and restricted and repetitive behaviours (RRB) as well as calibrated severity scores (CSS), a measure of severity of autism. Primary analysis included multivariable linear regression models to examine the predictive influence of sociodemographic and sociocultural factors on the dependant variables of age of concern (AOC) and the autism traits (SA, RRB, and CSS). RESULTS: The mean AOC in the sample was 18.18 months and the most common concerns were speech/language delay, limited social interaction, and hyperactivity/behavioural changes. The multivariable linear regression models showed factors such as increase in age of child, those from a CALD background, annual family income, sibling's autism diagnosis, and developmental concerns to be significantly associated with parental AOC. Additionally, we also found that increase in child's age and CALD status to be significant predictors of autism trait (RRB) and severity measured in terms of the CSS score. Further, females (compared to males) were associated with higher difficulties with social communication and interaction skills. CONCLUSION: Understanding key factors that contribute to early identification of autism can help tailor awareness programs for parents and caregivers, whilst also informing the development of services focused on serving all CALD communities.

General practitioners' perspectives regarding early developmental surveillance for autism within the australian primary healthcare setting: a qualitative study.

BACKGROUND: Significant challenges remain in the early identification of child developmental disabilities in the community. Implementing supports and services early in the life course has been shown to promote positive developmental outcomes for children at high likelihood of developmental disabilities, including autism. As part of a cluster randomised controlled trial, this study seeks to examine and compare the perspectives and experiences of Australian general practitioners (GPs) in relation to a digital developmental surveillance program for autism and usual care pathway, in general practice clinics. METHODS: A qualitative research methodology with semi-structured interviews and thematic inductive analysis underpinned by grounded theory was utilised. All GPs from South Western Sydney (NSW) and Melbourne (Victoria) who participated in the main program ("GP Surveillance for Autism") were invited to the interview. GPs who provided consent were interviewed either over online or in-person meeting. Interviews were audio-recorded, transcribed, and coded using NVivo12 software. Inductive interpretive approach was adopted and data were analysed thematically. RESULTS: Twenty-three GPs across the two sites (NSW: n = 11; Victoria: n = 12) agreed to be interviewed; data saturation had reached following this number of participants. Inductive thematic coding and analysis yielded eight major themes and highlighted common enablers such as the role of GPs in early identification and subsequent supports, enhanced communication between clinicians/professionals, relationship-building with patients, and having standardised screening tools. Specific facilitators to the feasibility and acceptability of a digital screening program for the early identification of developmental disabilities, including the early signs of autism, and encouraging research and education for GPs. However, several practical and socioeconomic barriers were identified, in addition to limited knowledge and uptake of child developmental screening tools as well as COVID-19 lockdown impacts. Common and specific recommendations involve supporting GPs in developmental/paediatrics training, streamlined screening process, and funding and resources in the primary healthcare services. CONCLUSIONS: The study highlighted the need for practice and policy changes, including further training of GPs alongside sufficient time to complete developmental checks and appropriate financial remuneration through a Medicare billing item. Further research is needed on implementation and scale up of a national surveillance program for early identification of developmental disabilities, including autism.

Screening for Media Use in the Emergency Department Among Young Australians: Cross-sectional Study.

BACKGROUND: Research on problematic internet use has largely adhered to addiction paradigms, possibly impeding the identification of specific internet behaviors related to psychopathology. This study presents a novel approach to screening for specific problematic internet behaviors by using a new measure, the emergency department media use screener (EDMUS). OBJECTIVE: The purpose of this study was to identify patterns of internet use in young people presenting with mental health concerns to the emergency department (ED), ascertain associations with their mental health, and evaluate whether the EDMUS can be used to predict subsequent ED presentations within 3 months. METHODS: This cross-sectional retrospective study of Australian young people (N=149, aged 11-25 years; female: n=92, 61.7%) sought to use the EDMUS, a 24-item questionnaire, to identify problematic internet behaviors, including accessing or posting prosuicidal or proeating disorder content, cyberbullying, and inappropriate digital content. Data on each person's mental health were extracted from electronic medical records to look for associations with EDMUS responses and ED re-presentation over 3 months. EDMUS items were grouped into clusters for analysis using chi-square tests, binary logistic regression, and path analyses. RESULTS: Sharing suicidal digital content was the most common problematic internet use pattern identified by the EDMUS. However, this did not correlate with having a prior mental health diagnosis or predict readmission. Most participants had families with a concern for their internet use; however, this was less likely in participants with a diagnosis of personality disorder. Diagnoses of personality disorder or posttraumatic stress disorder were independent predictors of readmission (P=.003; P=.048). CONCLUSIONS: Although a history of complex psychopathology increases the likelihood of subsequent ED presentations, its links to internet use-related behaviors are still unclear. The EDMUS has potential for identifying young people who are most vulnerable to problematic internet behaviors and offers the opportunity for early intervention and potential prevention of more entrenched difficulties.

Codesigning a social prescribing pathway to address the social determinant of health concerns of children with cerebral palsy and their families in Australia: a protocol for a mixed-methods formative research study.

INTRODUCTION: Social determinants of health (SDH) are contributors to health inequities experienced by some children with cerebral palsy and pose barriers to families engaging with complex and fragmented healthcare systems. There is emerging evidence to support 'social prescribing' interventions that systematically identify SDH concerns and refer patients to non-medical social care support and services to address their needs. To date, social prescribing has not been trialled specifically for children with neurodevelopmental disabilities, including cerebral palsy, in Australia. This study aims to codesign a social prescribing programme to address SDH concerns of children with cerebral palsy and their families who attend one of the three tertiary paediatric rehabilitation services in New South Wales, Australia. METHODS AND ANALYSIS: This is a qualitative multi-site study conducted at the three NSW paediatric hospitals' rehabilitation departments using a codesign approach. Children aged 12-18 years with cerebral palsy, parents/caregivers of children (aged 0-18 years) with cerebral palsy, and clinicians will be involved in all stages to codesign the social prescribing programme. The study will consist of three components: (1) 'what we need', (2) 'creating the pathways' and (3) 'finalising and sign off'. This project is overseen by two advisory groups: one group of young adults with cerebral palsy and one group of parents of young people with cerebral palsy. The study will be guided by the biopsychosocial ecological framework, and analysis will follow Braun and Clark's thematic approach. ETHICS AND DISSEMINATION: The study protocol was approved by the human research ethics committee of the Sydney Children's Hospitals Network. This codesign study will inform a future pilot study of feasibility and acceptability, then if indicated, a pilot clinical trial of efficacy. We will collaborate with all project stakeholders to disseminate findings and undertake further research to build sustainable and scalable models of care. TRIAL REGISTRATION NUMBER: ACTRN12622001459718.

Interactions between the lipidome and genetic and environmental factors in autism.

Autism omics research has historically been reductionist and diagnosis centric, with little attention paid to common co-occurring conditions (for example, sleep and feeding disorders) and the complex interplay between molecular profiles and neurodevelopment, genetics, environmental factors and health. Here we explored the plasma lipidome (783 lipid species) in 765 children (485 diagnosed with autism spectrum disorder (ASD)) within the Australian Autism Biobank. We identified lipids associated with ASD diagnosis (n = 8), sleep disturbances (n = 20) and cognitive function (n = 8) and found that long-chain polyunsaturated fatty acids may causally contribute to sleep disturbances mediated by the FADS gene cluster. We explored the interplay of environmental factors with neurodevelopment and the lipidome, finding that sleep disturbances and unhealthy diet have a convergent lipidome profile (with potential mediation by the microbiome) that is also independently associated with poorer adaptive function. In contrast, ASD lipidome differences were accounted for by dietary differences and sleep disturbances. We identified a large chr19p13.2 copy number variant genetic deletion spanning the LDLR gene and two high-confidence ASD genes (ELAVL3 and SMARCA4) in one child with an ASD diagnosis and widespread low-density lipoprotein-related lipidome derangements. Lipidomics captures the complexity of neurodevelopment, as well as the biological effects of conditions that commonly affect quality of life among autistic people.

Identification of subgroups of children in the Australian Autism Biobank using latent class analysis.

BACKGROUND: The identification of reproducible subtypes within autistic populations is a priority research area in the context of neurodevelopment, to pave the way for identification of biomarkers and targeted treatment recommendations. Few previous studies have considered medical comorbidity alongside behavioural, cognitive, and psychiatric data in subgrouping analyses. This study sought to determine whether differing behavioural, cognitive, medical, and psychiatric profiles could be used to distinguish subgroups of children on the autism spectrum in the Australian Autism Biobank (AAB). METHODS: Latent profile analysis was used to identify subgroups of children on the autism spectrum within the AAB (n = 1151), utilising data on social communication profiles and restricted, repetitive, and stereotyped behaviours (RRBs), in addition to their cognitive, medical, and psychiatric profiles. RESULTS: Our study identified four subgroups of children on the autism spectrum with differing profiles of autism traits and associated comorbidities. Two subgroups had more severe clinical and cognitive phenotype, suggesting higher support needs. For the 'Higher Support Needs with Prominent Language and Cognitive Challenges' subgroup, social communication, language and cognitive challenges were prominent, with prominent sensory seeking behaviours. The 'Higher Support Needs with Prominent Medical and Psychiatric and Comorbidity' subgroup had the highest mean scores of challenges relating to social communication and RRBs, with the highest probability of medical and psychiatric comorbidity, and cognitive scores similar to the overall group mean. Individuals within the 'Moderate Support Needs with Emotional Challenges' subgroup, had moderate mean scores of core traits of autism, and the highest probability of depression and/or suicidality. A fourth subgroup contained individuals with fewer challenges across domains (the 'Fewer Support Needs Group'). LIMITATIONS: Data utilised to identify subgroups within this study was cross-sectional as longitudinal data was not available. CONCLUSIONS: Our findings support the holistic appraisal of support needs for children on the autism spectrum, with assessment of the impact of co-occurring medical and psychiatric conditions in addition to core autism traits, adaptive functioning, and cognitive functioning. Replication of our analysis in other cohorts of children on the autism spectrum is warranted, to assess whether the subgroup structure we identified is applicable in a broader context beyond our specific dataset.

Spoken Language Change in Children on the Autism Spectrum Receiving Community-Based Interventions.

We assessed the spoken language of 73 preschool aged children on the autism spectrum receiving community-based early intervention at two time points, approximately 7 months apart. Using the Spoken Language Benchmarks, there was a small non-significant change in the proportion of children transitioning from below, to at or above, Phase 3 (word combinations). Using binomial regression, a model comprising seven of nine clinician-proposed child-related predictors explained 64% of the variance. None of the predictors were individually significant, although a large effect size (OR = 16.71) was observed for children's baseline rate of communicative acts. The findings point to substantial unmet clinical need in children with minimal verbal language, but also the relevance of clinician-proposed predictors of their spoken language outcomes.

Factors Impacting Parental Quality of Life in Preschool Children on the Autism Spectrum.

This study examined connections between parental quality of life (QoL) and features of children (autism severity, cognitive ability, behavioral profile, and sociodemographic factors). Parents of 97 children attending an autism-specific preschool completed the Quality of Life in Autism, Vineland Adaptive Behavior Scales and Child Behavior Checklist. The Autism Diagnostic Observation Schedule and Mullen Scales of Early Learning were also administered. Reduced restrictive/repetitive behavior and higher socialization and play/leisure scores were associated with better parental QoL. Better behavioral regulation and attention also predicted better QoL, as did stronger communication and reduced internalising behaviours. Findings indicate that a child's level of autism specific traits, adaptive functioning and behavioral profile has greater impact on parental QoL than cognitive level.

Parental experience of an early developmental surveillance programme for autism within Australian general practice: a qualitative study.

OBJECTIVES: Implementing support and services early in the life course has been shown to promote positive developmental outcomes for children at high likelihood of developmental conditions including autism. This study examined parents'/caregivers' experiences and perceptions about a digital developmental surveillance pathway for autism, the autism surveillance pathway (ASP), and usual care, the surveillance as usual (SaU) pathway, in the primary healthcare general practice setting. DESIGN: This qualitative study involves using a convenience selection process of the full sample of parents/caregivers that participated in the main programme, 'General Practice Surveillance for Autism', a cluster-randomised controlled trial study. All interviews were audio-recorded, transcribed and coded using NVivo V.12 software. An inductive thematic interpretive approach was adopted and data were analysed thematically. PARTICIPANTS: Twelve parents/caregivers of children with or without a developmental condition/autism (who participated in the main programme) in South Western Sydney and Melbourne were interviewed. SETTINGS: All interviews were completed over the phone. RESULTS: There were seven major themes and 20 subthemes that included positive experiences, such as pre-existing patient-doctor relationships and their perceptions on the importance of knowing and accessing early support/services. Barriers or challenges experienced while using the SaU pathway included long waiting periods, poor communication and lack of action plans, complexity associated with navigating the healthcare system and lack of understanding by general practitioners (GPs). Common suggestions for improvement included greater awareness/education for parents/carers and the availability of accessible resources on child development for parents/caregivers. CONCLUSION: The findings support the use of digital screening tools for developmental surveillance, including for autism, using opportunistic contacts in the general practice setting. TRIAL REGISTRATION NUMBER: ANZCTR (ACTRN12619001200178).

Dietary intake in children on the autism spectrum is altered and linked to differences in autistic traits and sensory processing styles.

Diets of children and adolescents on the autism spectrum often differ when compared to their non-autistic peers. Most dietary studies have been limited by small sample sizes and rarely assess the heterogeneity of autism. Addressing this gap, this study compared the anthropometrics, dietary composition, dietary quality, and food variety of 154 Australian children and adolescents on the spectrum and 213 non-autistic children (71 siblings and 142 unrelated controls). Beyond the case-control approach, within-group comparisons assessed the influence of autism clinical presentations and sensory processing styles on body mass index (BMI) and measures of dietary intake among those on the spectrum. In this word first study of diet that included between-group comparisons with non-autistic peers (siblings and an unrelated comparison group) and within-autism group comparisons, we found that children on the spectrum consumed limited variety and lower quality of food and non-autistic siblings also ate comparably higher levels of energy-dense, nutrient poor food, and less diary. This may be due to autistic traits influencing family's diets or shared sensory sensitivities driving dietary intake. Within the autism group, higher autistic traits were associated with lower BMIs and a specific dietary pattern higher in simple carbohydrates and lower in unprocessed protein. Contrastingly, greater sensitivity to sensory stimuli was associated with a healthier diet. Increased age was linked to more varied diets but also diets higher in saturated fats and energy-dense, nutrient poor foods. Overall, this research highlights that potential mediators of dietary intake, such as familial influences, autistic traits, sensory processing styles, age and sex, need to be considered when assessing diet in the autistic population. LAY SUMMARY: In this study of dietary differences linked to autism, children, and teenagers on the spectrum ate fewer different foods and were less likely to eat recommended amounts of fruits and vegetables when compared to non-autistic siblings and unrelated children and teenagers. There were also family differences, in that those on the spectrum and their siblings ate more unhealthy foods and less dairy. Among those on the spectrum, dietary differences were linked to age, sex, autistic traits and sensory processing styles.

A systematic review of the biological, social, and environmental determinants of intellectual disability in children and adolescents.

Aim: This systematic review aimed to identify the most important social, environmental, biological, and/or genetic risk factors for intellectual disability (ID). Methods: Eligible were published prospective or retrospective comparative studies investigating risk factors for ID in children 4-18 years. Exclusions were single group studies with no comparator without ID and a sample size <100. Electronic databases (Medline, Cochrane Library, EMBASE, PsycInfo, Campbell Collaboration, and CINAHL) were searched for eligible publications from 1980 to 2020. Joanna Briggs Institute critical appraisal instruments, appropriate for study type, were used to assess study quality and risk of bias. Descriptive characteristics and individual study results were presented followed by the synthesis for individual risk factors, also assessed using GRADE. Results: Fifty-eight individual eligible studies were grouped into six exposure topics: sociodemographic; antenatal and perinatal; maternal physical health; maternal mental health; environmental; genetic or biological studies. There were few eligible genetic studies. For half the topics, the certainty of evidence (GRADE) was moderate or high. Conclusion: Multiple studies have examined individual potential determinants of ID, but few have investigated holistically to identify those populations most at risk. Our review would indicate that there are vulnerable groups where risk factors we identified, such as low socioeconomic status, minority ethnicity, teenage motherhood, maternal mental illness, and alcohol abuse, may cluster, highlighting a target for preventive strategies. At-risk populations need to be identified and monitored so that interventions can be implemented when appropriate, at preconception, during pregnancy, or after birth. This could reduce the likelihood of ID and provide optimal opportunities for vulnerable infants. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=120032], identifier [CRD42019120032].

Genetic Pathways Associated With Sleep Problems in Children With Autism Spectrum Disorder.

Aims: Children on the autism spectrum are more likely to have sleep problems than non-autistic children. Sleep disturbance may exacerbate emotional and behavioral problems of children on the autism spectrum. A better understanding of the biological mechanisms underlying sleep disturbance provide clues to better management for this co-morbid condition in autism. The goal of the current study is to identify genetic variants associated with sleep disturbance and melatonin levels in autistic children. Methods: A total of 969 children on the autism spectrum were genotyped using the Global Screening Array v1 or Global Screening Array v2. Sleep problems were assessed using the Children's Sleep Habits Questionnaire (CSHQ). Melatonin levels were measured using the urine samples of 219 probands. The relationship between the melatonin level and CSHQ score was examined using the general linear model. The genetic variants associated with the CSHQ score and melatonin level as two separate quantitative traits were determined using genomewide association studies. Results: The data indicates that urine melatonin levels were positively associated with CSHQ scores, suggesting that autistic children with a poorer sleep qualiy could has higher melatonin level. Furthermore, genetic assocication studies suggest that genetic pathways involved in pro-inflammatory responses might be involved in sleep disturbance, while genetic pathways involved in catecholamine-secreting PC12 cells and Schwann cells could be associated with melatonin levels. Conclusions: Taken together, our findings indicate that sleep disturbance and melatonin metabolism could be attributable to distinct biological mechanisms in autistic children since they might not share genetic contributors.